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World J Radiol. Jul 28, 2014; 6(7): 480-485
Published online Jul 28, 2014. doi: 10.4329/wjr.v6.i7.480
Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters
Hinrich A Wieder, Michael Lassmann, Martin S Allen-Auerbach, Johannes Czernin, Ken Herrmann
Hinrich A Wieder, Department of Radiology, Zentrum für Radiologie und Nuklearmedizin, 41515 Grevenbroich, Germany
Hinrich A Wieder, Department of Nuclear Medicine, Technische Universität München, 81675 Munich, Germany
Michael Lassmann, Ken Herrmann, Department of Nuclear Medicine, University of Würzburg, 97080 Würzburg, Germany
Martin S Allen-Auerbach, Johannes Czernin, Ahmanson Translational Imaging Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, United States
Author contributions: Wieder HA, Lassmann M, Allen-Auerbach M, Czernin J and Herrmann K contributed to development of outline, and revision and approval of manuscript; Wieder HA, Czernin J and Herrmann K contributed to drafting and editing of manuscript; Lassmann M and Allen-Auerbach M contributed to figures.
Correspondence to: Hinrich A Wieder, MD, Department of Radiology, Zentrum für Radiologie und Nuklearmedizin, Zentrum für Radiologie und Nuklearmedizin, Von-Werth-Straße 5, 41515 Grevenbroich, Germany.
Telephone: +49-2133-664980 Fax: +49-2133-662983
Received: November 27, 2013
Revised: March 20, 2014
Accepted: May 16, 2014
Published online: July 28, 2014

Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit β-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available. In contrast to β-emitters, 223Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity. The α emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the 223Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in pain palliation and thus, improved quality of life and a delay of skeletal related events. At the same time the toxicity profile of 223Radium was favourable. Since May 2013, 223Radium dichloride (Xofigo®) is approved by the US Food and Drug Administration.

Keywords: Radium, Bone targeted radiopharmaceuticals, Alpha emitters

Core tip: The incidence rate of prostate cancer worldwide is high. Ninety percent of patients dying of prostate cancer have bone metastases with varying symptoms which are significantly impairing their quality of life. 223Radium is the first therapeutic that results in a survival benefit for patients with bone metastatic, castrate resistant prostate cancer. 223Radium was also associated with low myelosuppression rates and fewer adverse events.This article provides an overview of the pre-clinical and clinical trials with 223Radium.